Carter, Rickey E

Abstract Rationale Acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. Objectives To determine select peripheral blood lipid mediator and leukocyte responses in patients at risk for ARDS. Methods Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (the LIPS-A [Lung Injury Prevention Study with Aspirin] trial; NCT01504867). Plasma thromboxane B2 (TXB2), aspirin-triggered lipoxin A4 (15-epi-LXA4, ATL), and peripheral blood leukocyte number and activation were determined on enrollment and after treatment with either aspirin or placebo. Measurements and Main Results Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte counts, and monocyte–platelet aggregates were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte–platelet aggregates significantly decreased over time. Of note, nine subjects developed ARDS after randomization yet before study drug initiation, including seven subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TXB2 and increased the ATL/TXB2 ratio. Conclusions Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS and represent potential vascular biomarkers of ARDS risk. Clinical trial registered with www.clinicaltrials.gov (NCT01504867).

Abstract This Consensus Document is the first of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the clinical use of intracoronary imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The first document appraises the role of intracoronary imaging to guide percutaneous coronary interventions (PCIs) in clinical practice. Current evidence regarding the impact of intracoronary imaging guidance on cardiovascular outcomes is summarized, and patients or lesions most likely to derive clinical benefit from an imaging-guided intervention are identified. The relevance of the use of IVUS or OCT prior to PCI for optimizing stent sizing (stent length and diameter) and planning the procedural strategy is discussed. Regarding post-implantation imaging, the consensus group recommends key parameters that characterize an optimal PCI result and provides cut-offs to guide corrective measures and optimize the stenting result. Moreover, routine performance of intracoronary imaging in patients with stent failure (restenosis or stent thrombosis) is recommended. Finally, strengths and limitations of IVUS and OCT for guiding PCI and assessing stent failures and areas that warrant further research are critically discussed.

ABSTRACTIntroduction: For sequential and somatotopic assessment of small fiber neuropathy, heat pain (HP) tests of hypoalgesia might be used instead of decreased counts of epidermal nerve fibers (ENFs), but then healthy subject reference values of HP thresholds are needed. Methods: Using the Computer Assisted Sensation Evaluator IVc system, HP thresholds of hypoalgesia were estimated for 10 unilateral sites and counts of ENFs for 4 of them in healthy subjects. Results: In healthy subjects, small but statistically significant differences of both HP thresholds of hypoalgesia and counts of ENFs were observed among tested sites. Significant correlations between HP thresholds and counts of ENFs were not found. Discussion: For the studied somatotopic sites, we provide ≥95th and ≥99th percentile reference limits for HP 0.5 and 5 of 1–10 HP thresholds of hypoalgesia and decreased counts of ENFs at ≤5th and ≤1st percentile levels. Muscle Nerve 58: 509–516, 2018

Introduction Clinical practice guidelines facilitate optimal clinical practice. Point of care access, interpretation and application of such guidelines, however, is inconsistent. Informatics-based tools may help clinicians apply guidelines more consistently. We have developed a novel clinical decision support tool that presents guideline-relevant information and actionable items to clinicians at the point of care. We aim to test whether this tool improves the management of hyperlipidaemia, atrial fibrillation and heart failure by primary care clinicians. Methods/analysis Clinician care teams were cluster randomised to receive access to the clinical decision support tool or passive access to institutional guidelines on 16 May 2016. The trial began on 1 June 2016 when access to the tool was granted to the intervention clinicians. The trial will be run for 6 months to ensure a sufficient number of patient encounters to achieve 80% power to detect a twofold increase in the primary outcome at the 0.05 level of significance. The primary outcome measure will be the percentage of guideline-based recommendations acted on by clinicians for hyperlipidaemia, atrial fibrillation and heart failure. We hypothesise care teams with access to the clinical decision support tool will act on recommendations at a higher rate than care teams in the standard of care arm. Ethics and dissemination The Mayo Clinic Institutional Review Board approved all study procedures. Informed consent was obtained from clinicians. A waiver of informed consent and of Health Insurance Portability and Accountability Act (HIPAA) authorisation for patients managed by clinicians in the study was granted. In addition to publication, results will be disseminated via meetings and newsletters. Trial registration number NCT02742545 .

Background: Glucose variability (GV) has been increasingly (or more extensively) studied in patients with type 1 diabetes (T1D) in the ambulatory setting; limited data exist on GV in hospitalized patients with T1D. Materials and Methods: Retrospective single center cohort study, we analyzed in-hospital glucose measurements to assess GV in 736 hospitalized patients in different units over a consecutive 5-year period of time. GV was assessed by mean blood glucose (BG), Average daily risk range (ADRR), high BG index, and low BG index. To place our findings in context, we conducted a systematic review using Cochrane collaboration methodology to critically analyze current published literature on GV in hospitalized T1D patients. Results: Overall, glycemic control was suboptimal with mean BG 183 ± 51.5 mg/dL and mean ADRR 35 with only 16% patients being categorized as low risk (ADRR <20) for hypo or hyperglycemia. Patients admitted in medical units had mean BG of 194.4 ± 42.8 mg/dL (95% CI = 101.2–346.6) and ADRR of 39.4 ± 16 (95% CI = 1.3–118.7), which were higher than the patients admitted in the surgical units (mean BG 168.1 ± 35.7 (95% CI = 74.8–301.8) and mean ADRR (28.8 ± 13.1 [95% CI = 0.3–93.1]). For the systematic review, initial search yielded 2336 studies for screening, however, none of them had data specific for T1D. Conclusion: GV is high in hospitalized T1D patients admitted at our tertiary care center. Review of the literature shows paucity of data regarding GV in hospitalized patients with T1D.

OBJECTIVE Artificial pancreas (AP) systems are best positioned for optimal treatment of type 1 diabetes (T1D) and are currently being tested in outpatient clinical trials. Our consortium developed and tested a novel adaptive AP in an outpatient, single-arm, uncontrolled multicenter clinical trial lasting 12 weeks. RESEARCH DESIGN AND METHODS Thirty adults with T1D completed a continuous glucose monitor (CGM)-augmented 1-week sensor-augmented pump (SAP) period. After the AP was started, basal insulin delivery settings used by the AP for initialization were adapted weekly, and carbohydrate ratios were adapted every 4 weeks by an algorithm running on a cloud-based server, with automatic data upload from devices. Adaptations were reviewed by expert study clinicians and patients. The primary end point was change in hemoglobin A1c (HbA1c). Outcomes are reported adhering to consensus recommendations on reporting of AP trials. RESULTS Twenty-nine patients completed the trial. HbA1c, 7.0 ± 0.8% at the start of AP use, improved to 6.7 ± 0.6% after 12 weeks (−0.3, 95% CI −0.5 to −0.2, P &lt; 0.001). Compared with the SAP run-in, CGM time spent in the hypoglycemic range improved during the day from 5.0 to 1.9% (−3.1, 95% CI −4.1 to −2.1, P &lt; 0.001) and overnight from 4.1 to 1.1% (−3.1, 95% CI −4.2 to −1.9, P &lt; 0.001). Whereas carbohydrate ratios were adapted to a larger extent initially with minimal changes thereafter, basal insulin was adapted throughout. Approximately 10% of adaptation recommendations were manually overridden. There were no protocol-related serious adverse events. CONCLUSIONS Use of our novel adaptive AP yielded significant reductions in HbA1c and hypoglycemia.

Purpose Using common datasets, to estimate and compare the diagnostic performance of image‐based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic metastases. Methods Datasets from contrast‐enhanced CT scans of the liver were provided to participants in an NIH ‐, AAPM ‐ and Mayo Clinic‐sponsored Low Dose CT Grand Challenge. Training data included full‐dose and quarter‐dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor‐neutral standardized format ( DICOM ‐ CT ‐ PD ). Twenty quarter‐dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter‐dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per‐lesion normalized score and a per‐case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per‐lesion and per‐case normalized score). Reader confidence was used to compute a Jackknife alternative free‐response receiver operating characteristic ( JAFROC ) figure of merit, which was used for breaking ties. Results 103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data ( CTDI vol = 3.0 ± 1.8 mG y, SSDE = 3.5 ± 1.3 mG y). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per‐lesion and per‐case normalized scores were −24.2% (−75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter‐dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full‐dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing. Conclusion Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low‐dose CT examinations of the liver after either image‐based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter‐dose images with no noise reduction applied.

Aim To describe the impact of steps towards reduction of procedural doses of radiation during neuroendovascular procedures. Methods Phantom exposures under controlled circumstances were performed using a Rando-Alderson adult-sized head phantom. Customized imaging protocols were devised for pediatric and adult imaging and implemented in clinical use. Outcome data for estimated skin doses (ESD) and dose–area product (DAP) following pediatric and adult diagnostic and interventional procedures over 4.5 years were analyzed retrospectively. Results Dose estimates were reduced by 50% or more after introduction of customized imaging protocols in association with modification of personnel behavior compared with doses recorded with previously used vendor-recommended protocols. Discussion Substantial reductions in radiation use during neuroendovascular procedures can be achieved through a combination of equipment modification and operator behavior.